Overlapping homologous superfamilies

Family relationships

Description

Thrombin belongs to the MEROPS peptidase family S1, subfamily S1A.

Prothrombin consists of an N-terminal gamma-carboxyglutamate (GLA) domain, two kringle domains, and the S1A peptidase catalytic domain. The cleavage of prothrombin to thrombin is catalysed by the prothrombinase enzyme complex that consists of serine protease factor Xa, cofactor Va, phospholipids and calcium. Prothromin is cleaved by this enzyme into three fragments: fragment 1 (F1) consits of the GLA domain and the first Kringle domain; fragment 2 (F2) consists of the second Kringle domain; and thrombin (peptidase catalytic domain). F1 facilitates calcium-dependent binding of the proenzyme to phospholipid surfaces. F2 interacts with factor Va, and once it is released from prothrombin, it can bind thrombin to influence its function [PMID: 9535876].

Thrombin is a member of the trypsin family of S1 peptidases. It catalyses the preferential cleavage of arginine-lysine bonds, converting fibrinogen to fibrin, and releasing fibrinopeptides A and B. Thrombin can itself cleave the N-terminal fragment (fragment 1) of prothrombin, prior to its activation by factor Xa. Its effects are mediated by the thrombin receptor. Structures of the thrombin A-chain [PMID: 2583108] and B-chain [PMID: 10051558] have been determined. The most conserved portions of the B chain are the active-site residues and adjacent amino acids, the B loop, and the primary substrate-binding region [PMID: 1557383]. The extent of sequence similarity between species and the conservation of many of the functional/structural motifs suggests that, in addition to their role in blood coagulation, vertebrate thrombins may play an important role in the general mechanisms of wound repair [PMID: 1557383].